ACTIVE-SITES OF LIGANDS AND THEIR RECEPTORS ARE MADE OF COMMON PEPTIDES THAT ARE ALSO FOUND ELSEWHERE

The simultaneous emergence in evolution of a Ligand and its receptor m ight have entailed their active sites being drawn from the pool of com mon oligopeptides. This was tested on the principal components of cell -matrix interaction: the RGD (Arg-Gly-Asp) site of matrix proteins and the EKKD (Gly-Lys-Lys-Asp) site of integrin cell-surface receptor. In the 32 diverse proteins scrutinized, which totalled 14,806 residues, there were 104 Arg-Gly dipeptides. Most common of the tripeptides begi nning with Arg-Gly were Arg-Gly-Leu, Arg-Gly-Gly, and Arg-Gly-Asp; eac h was found in ten copies. RGD tripeptide was one of the commonest; th e fortuitous presence of an RGD site was noted in two enzymes, fibrino gen, a pituitary hormone precursor, and a viral structural protein. Th e 32 proteins also contained 121 Lys-Lys dipeptides. Of the tetrapepti des centered by Lys-Lys, the commonest was Lys-Lys-Lys-Lys, in four co pies. Second most common were Gly-Lys-Lys-Lys, Val-Lys-Lys-Leu, and Gl u-Lys-Lys-Asp; each occurred in three copies. The fortuitous presence of an EKKD site was noted in three proteins-an intracellular transport protein, a pituitary hormone precursor and a protein of the cerebrosp inal fluid. In most instances, protein-protein interaction between the fortuitously present active sites appears to bring about deleterious consequences. Occasionally, however, the fortuitous active site appear s to confer a new function to a protein bearing it.